POTENTIAL ROLE OF THE FLAVIN-CONTAINING MONOOXYGENASES IN THE METABOLISM OF ENDOGENOUS COMPOUNDS
POTENTIAL ROLE OF THE FLAVIN-CONTAINING MONOOXYGENASES IN THE METABOLISM OF ENDOGENOUS COMPOUNDS
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DOI：
10.1016/0009-2797(94)03582-s
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发表时间：
1995-04-28
影响因子：
5.1
通讯作者：
ELFARRA, AA
中科院分区：
文献类型：
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作者：
ELFARRA, AA
几种异生素及其相应的半胱氨酸 S-缀合物在体内代谢为半胱氨酸 S-缀合物亚砜和/或 N-乙酰半胱氨酸 S-缀合物亚砜。同型半胱氨酸 S-结合物，例如甲硫氨酸和乙硫氨酸，也在体内代谢为亚砜。这些代谢反应的酶促基础尚不清楚。最近，发现大鼠肝脏和肾脏 S-苄基-L-半胱氨酸 S-氧化酶活性与含黄素单加氧酶相关，而含黄素单加氧酶在结构和免疫化学上与已知的 FMO1 亚型相关。从 cDNA 表达的兔 FMO 的动力学研究中获得了 FMO1 是参与 S-苄基-L-半胱氨酸磺化氧化的主要 FMO 亚型的进一步证据。内源性半胱氨酸 S-缀合物，例如半胱氨酰儿茶酚胺、半胱氨酰白三烯、羊毛硫氨酸和二烯可酸也可能是 FMO 的底物，因为 S-苄基-L-半胱氨酸可被视为这些化合物的模型。蛋氨酸是一种内源性同型半胱氨酸 S-结合物，被证明是 cDNA 表达的兔 FMO1、FMO2 和 FMO3 的底物，然而，蛋氨酸磺化反应优先由 FMO3 催化。这些结果表明 FMO 也可能在内源性同型半胱氨酸 S-缀合物的体内代谢中发挥作用。
Several xenobiotics and their corresponding cysteine S-conjugates are metabolized in vivo to cysteine S-conjugate sulfoxides and/or N-acetylcysteine S-conjugate sulfoxides. Homocysteine S-conjugates, such as methionine and ethionine, are also metabolized in vivo to sulfoxides. The enzymatic basis for these metabolic reactions is not known. Recently, the rat liver and kidney S-benzyl-L-cysteine S-oxidase activities were found to be associated with flavin-containing monooxygenases that are structurally and immunochemically related to known FMO1 isoforms. Further evidence for FMO1 being the major FMO isoform involved in S-benzyl-L-cysteine sulfoxidation was obtained from kinetic studies with cDNA-expressed rabbit FMOs. Endogenous cysteine S-conjugates, e.g. cysteinylcatecholamines, cysteinylleukotrienes, lanthionine and djenkolic acid may also be substrates for FMOs, since S-benzyl-L-cysteine can be considered a model for these compounds. Methionine, an endogenous homocysteine S-conjugate, was shown to be a substrate for cDNA-expressed rabbit FMO1, FMO2, and FMO3, however, the methionine sulfoxidation reaction was preferentially catalyzed by FMO3. These results suggest that FMOs may also play a role in the in vivo metabolism of endogenous homocysteine S-conjugates.